Norovirus major capsid protein VP1 protruding domain (VP1 P-domain) (VP1 P-domain)

The Norovirus VP1 P-domain is the outermost part of the major capsid protein (VP1) of noroviruses, which are the leading cause of acute viral gastroenteritis worldwide (Tan & Jiang, 2014, PMID: 24501066). This domain is structurally divided into P1 and P2 subdomains, with the P2 subdomain being highly variable and containing the binding sites for histo-blood group antigens (HBGAs) (Mallagaray et al., 2019, PMID: 30643021). HBGAs serve as essential attachment factors or co-receptors for viral entry into host cells (Marionneau et al., 2002, PMID: 11831716). Because it is the most exposed portion of the virus, the P-domain is the primary target for neutralizing antibodies and is a critical focus for vaccine development, including virus-like particles (VLPs) and P-particle platforms (Jiang et al., 1992, PMID: 1310514). Therapeutic strategies targeting the P-domain aim to inhibit viral infection by using small-molecule HBGA mimetics or monoclonal antibodies that sterically block the receptor-binding interface (Koromyslova et al., 2017, PMID: 28424244). However, the high degree of genetic diversity and rapid antigenic drift within the P-domain present significant challenges for the development of broadly protective vaccines and antivirals (Debbink et al., 2012, PMID: 22933273). Current research focuses on identifying conserved epitopes within the P-domain to create cross-reactive therapeutics that can overcome the challenges of viral evolution (Lindesmith et al., 2012, PMID: 22532665).

Other names

VP1 P-domainProtruding domain of VP1Norovirus P-domainP-domain of major capsid protein

Competitive inhibition of host cell attachment by blocking the P-domain's interaction with histo-blood group antigens (HBGAs).